During the past three decades much has been learned about the etiology, pathophysiology and natural history of cardiac disease. However, more than 60 percent of all deaths continue to be due to pathology of the heart and blood vessels. While rational therapeutic approaches to the management of several cardiac disorders have been developed, many new drugs and surgical techniques are becoming available almost daily for treating heart disease. The primary purpose of this program is to investigate the mechanism of actions of these therapies, to develop better understandings of how treatment alters the pathophysiology of heart disease, to establish interrelationships between biochemical actions of drugs and their physiologic actions, to determine the pathophysiologic principles necessitating surgical or drug therapy for a number of cardiac disorders, to document the efficacy of therapy in some cardiac disorders, and to assess the interactions between the many pharmacologic agents administered to a single cardiac patient. Interrelationships of blood levels, distribution, kinetics of administration, and metabolism with hemodynamic electrophysiologic and clinical effects will be investigated. New techniques for evaluating cardiac performance longitudinally will be developed and validated. The drug groups which will be assessed include antiarrhythmic agents, cardiac glycosides, inotropic agents, adrenergic blocking drugs, and analgesics. The effects of valve replacement and coronary artery vein bypass procedures will be determined. The overall goal of this program is to establish an improved and rational pharmacologic and physiologic basis for the treatment of many types of heart disease.